A total of 251 patients were randomized (median age, 51 [IQR, 34-69] years; 111 women [44.9%] and 140 men [55.1%] among the 247 with data available) and were included in the intention-to-treat population. The mean pain score change was −3.7 (95% CI, −4.2 to −3.2) in the ketamine group compared with −3.8 (95% CI, −4.2 to −3.4) in the morphine group. The difference in mean pain score change was 0.1 (95% CI, −0.7 to 0.9) points. There were no clinically meaningful differences for vital signs between the 2 groups. The intravenous morphine group had 19 of 113 (16.8% [95% CI, 10.4%-25.0%]) adverse effects reported (most commonly nausea [12 of 113 (10.6%)]) compared with 49 of 120 (40.8% [95% CI, 32.0%-49.6%]) in the ketamine group (most commonly emergence phenomenon [24 of 120 (20.0%)]). No adverse events required intervention.

Conclusions and Relevance In the KETAMORPH study of patients with out-of-hospital traumatic pain, the use of intravenous ketamine compared with morphine showed noninferiority for pain reduction. In the ongoing opioid crisis, ketamine administered alone is an alternative to opioids in adults with out-of-hospital traumatic pain.

El ensayo MUSIK descubrió que la música disminuía significativamente los cambios de la PA sistólica inducidos por la ketamina. Por lo tanto, la música puede representar un enfoque factible, benigno y no farmacológico para mejorar la respuesta hemodinámica de las infusiones subanestésicas de ketamina para el TRD. Los resultados secundarios del ensayo se publicarán en otro lugar.

Beyond psychiatric contexts, the stimulatory hemodynamic effects of ketamine have received extensive study, both as desirable (eg, in surgical contexts) and as potentially harmful (eg, in procedural sedation),5 but never in relation to music, to our knowledge. The magnitude of the hemodynamic effects observed in this study suggests that ketamine research should consider potential influences of contextual factors, including auditory stimuli. Ketamine’s unique psychoactive effects may amplify the effects of music and other environmental influences, as has been long observed in the anesthesiology literature.6

Although the MUSIK trial administered 181 ketamine infusions, its modest sample size is a limitation. Further investigation is needed in larger samples and additional clinical contexts.

Out of 782 studies retrieved from electronic databases, 11 met the inclusion criteria. Among them, 10 studies were retrospective, and 1 study was prospective. Patient data for inclusion were sourced from the case registries of the researchers' respective hospitals. Across all included studies, the administration of ketamine significantly reduced the duration of status epilepticus and demonstrated higher safety compared to patients not receiving ketamine treatment for super-refractory status epilepticus. Additionally, early administration of ketamine correlated with improved treatment outcomes. The risk of bias across all studies was deemed low.

The potential for ketamine to replicate NDE’s has been supported by research. A recent study published in Science Direct, looking at over 15,000 self-reports, found that the use of ketamine, over all other psychedelic compounds, most frequently led users to have NDE’s (followed by salvia in second and peyote in third). “After assessing the semantic similarity between 15,000 reports linked to the use of 165 psychoactive substances and 625 NDE narratives, we determined that the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine consistently resulted in reports most similar to those associated with NDE’s.” The authors go on to suggest that “ketamine could be used as a safe and reversible experimental model for NDE phenomenology”1

Within 1 h of ketamine dosing, patients reported reduced depression and anxiety ratings, which persisted for up to 7 days. A dose–response profile for ketamine was noted for dissociative side effects, adverse events and changes in blood pressure; however, changes in mood ratings were broadly similar for both ketamine doses. Overall, 14/25 patients (56%) were responders (⩾50% reduction at 24 h compared with baseline) for either ketamine dose for the Hospital Anxiety and Depression Scale (HADS), and 18/25 (72%) were responders for the HADS-anxiety scale. After fentanyl, only 1/25 (HADS-depression) and 3/25 (HADS-anxiety) were responders. Ketamine was generally safe and well tolerated in this population.

Conclusions:

Our findings add to the literature confirming ketamine’s activity against depressive and anxiety symptoms in patients with TRD.

This scoping review describes the existing literature on the joint use of music and ketamine-or esketamine (the S(+) enantiomer of ketamine)-in humans. The review considers that extant studies have explored the intersection of ketamine/esketamine and music in healthy volunteers and in patients of various age groups, at different dosages, through different treatment processes, and have varied the sequence of playing music relative to ketamine/esketamine administration.

An evolving overview of cognitive behavioral therapy in psychedelic-assisted psychotherapy and ketamine psychedelic therapy.

Esketamine and psilocybin NNT (number to treat) suggests safety and efficacy for depression

A low number to treat and a high number to harm (NNT and NNH, respectively), suggests ketamine treatment efficacy and safety.

Ketamine is currently widely used for analgesia and anesthesia in the care of military service members and its use has increased in combat zones of Iraq and Afghanistan due to the favorable preservation of respiratory function, minimal changes in hemodynamics, and lower pain scores compared to opioids. Ketamine acts as a non-competitive antagonist on N-methyl-D aspartate (NMDA) receptors. Its anesthesia and analgesic effects are complex and include both presynaptic and postsynaptic neurons in brain and spinal cord. The use of palliative care to minimize suffering should not be withheld due to the logistical boundaries of austere military environments or lack of guidelines for recommended use. The use of ketamine for palliative care is a new clinical management strategy to provide both sedation and pain management for an acute pain crisis or comfort measures for the terminally ill. This makes ketamine an attractive consideration for palliative care when managing critically wounded patients for an extended time.

…subanaesthetic doses of ketamine have been demonstrated to have rapid and sustained antidepressant effects, and accumulating research has demonstrated ketamine's therapeutic effects for a range of psychiatric conditions.

Among this sample, IV ketamine therapy appeared well tolerated and highly acceptable (mean 9.5 on 0–10 Likert scale). The mean Clinician-Administered Dissociative States Scale (CADSS) score was 21.7 (out of max 92). It seemed to occasion experiences that were largely positive, transporting, visual, and meaningful. The most frequently assigned themes in our data set were “Meaningful, spiritual, and mystical experiences,” “Positive affect,” and “Inherent contradictions of the acute experience.”

KAP produced sustained reductions in anxiety, depression, and PTSD, with symptom improvement lasting well beyond the duration of dosing and integration sessions. These effects extended to as much as 5 months after the last KAP session. However, the high rates of attrition may limit validity of the results. Given the growing mental health care crises and the need for effective therapies and models of care, especially for intractable psychiatric mood-related disorders, these data support the use of KAP as a viable alternative. Further prospective clinical research should be undertaken to provide evidence on the safety and effectiveness of ketamine within a psychotherapeutic context.

Currently, ketamine is used in treating multiple pain, mental health, and substance abuse disorders due to rapid-acting analgesic and antidepressant effects. Its limited short-term durability has motivated research into the potential synergistic actions between ketamine and psychotherapy to sustain benefits. This systematic review on ketamine-assisted psychotherapy (KAP) summarizes existing evidence regarding present-day practices. Through rigorous review, seventeen articles that included 603 participants were identified. From available KAP publications, it is apparent that combined treatments can, in specific circumstances, initiate and prolong clinically significant reductions in pain, anxiety, and depressive symptoms, while encouraging rapport and treatment engagement, and promoting abstinence in patients addicted to other substances. Despite much variance in how KAP is applied (route of ketamine administration, ketamine dosage/frequency, psychotherapy modality, overall treatment length), these findings suggest psychotherapy, provided before, during, and following ketamine sessions, can maximize and prolong benefits. Additional large-scale randomized control trials are warranted to understand better the mutually influential relationships between psychotherapy and ketamine in optimizing responsiveness and sustaining long-term benefits in patients with chronic pain. Such investigations will assist in developing standardized practices and maintenance programs.

Current research suggests that ketamine-assisted psychotherapy has benefit for the treatment of mental disorders. We report on the results of ketamine-assisted intensive outpatient psychotherapeutic treatment of a client with treatment-resistant, posttraumatic stress disorder (PTSD) as a result of experiences of racism and childhood sexual abuse. The client’s presenting symptoms included hypervigilance, social avoidance, feelings of hopelessness, and intense recollections. These symptoms impacted all areas of daily functioning. Psychoeducation was provided on how untreated intergenerational trauma, compounded by additional traumatic experiences, potentiated the client’s experience of PTSD and subsequent maladaptive coping mechanisms. Ketamine was administered four times over a 13-day span as an off-label, adjunct to psychotherapy. Therapeutic interventions and orientations utilized were mindfulness-based cognitive therapy (MBCT) and functional analytic psychotherapy (FAP). New skills were obtained in helping the client respond effectively to negative self-talk, catastrophic thinking, and feelings of helplessness. Treatment led to a significant reduction in symptoms after completion of the program, with gains maintained 4 months post-treatment. This case study demonstrates the effective use of ketamine as an adjunct to psychotherapy in treatment-resistant PTSD.

A central question in neuroscience is how consciousness arises from the dynamic interplay of brain structure and function. Here we decompose functional MRI signals from pathological and pharmacologically-induced perturbations of consciousness into distributed patterns of structure-function dependence across scales: the harmonic modes of the human structural connectome. We show that structure-function coupling is a generalisable indicator of consciousness that is under bi-directional neuromodulatory control. We find increased structure-function coupling across scales during loss of consciousness, whether due to anaesthesia or brain injury, capable of discriminating between behaviourally indistinguishable sub-categories of brain-injured patients, tracking the presence of covert consciousness. The opposite harmonic signature characterises the altered state induced by LSD or ketamine, reflecting psychedelic-induced decoupling of brain function from structure and correlating with physiological and subjective scores. Overall, connectome harmonic decomposition reveals how neuromodulation and the network architecture of the human connectome jointly shape consciousness and distributed functional activation across scales.