Efficacy, Safety, and Durability of Repeated Ketamine Infusions for Comorbid Posttraumatic Stress Disorder and Treatment-Resistant Depression

Albott, C. Sophia; Lim, Kelvin O.; Forbes, Miriam K.; Erbes, Christopher R.; Tye, Susannah J.; Grabowski, John; Thuras, Paul; Batres-Y-Carr, Tegan; Wels, Joseph; Shiroma, Paulo

doi:10.4088/jcp.17m11634

Cited by 114 publications

(90 citation statements)

References 27 publications

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“…Timothy Leary, a key figure in the popularization and subsequent stigmatization of LSD, referred to ketamine experiences as "experiments in voluntary death" (Jansen, 1997a(Jansen, ,1997b. It must be noted that the comparison between the experiences induced by these drugs and dying occurs at a purely psychological level, since these substances are very safe under most circumstances (Alberich et al, 2017;Albott et al, 2018;Dos Santos, Bouso, Alcázar-Córcoles, & Hallak, 2018;dos Santos, 2013;Gasser et al, 2014;Glue et al, 2018;Kyzar et al, 2017;Nichols, 2016;Rabi, 2016;Riva-Posse et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Neurochemical models of near-death experiences: A large-scale study based on the semantic similarity of written reports

Martial

Cassol

Charland‐Verville

et al. 2019

Consciousness and Cognition

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The real or perceived proximity to death often results in a non-ordinary state of consciousness characterized by phenomenological features such as the perception of leaving the body boundaries, feelings of peace, bliss and timelessness, life review, the sensation of traveling through a tunnel and an irreversible threshold. Near-death experiences (NDEs) are comparable among individuals of different cultures, suggesting an underlying neurobiological mechanism. Anecdotal accounts of the similarity between NDEs and certain drug-induced altered states of consciousness prompted us to perform a large-scale comparative analysis of these experiences. 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 NDEs. Ketamine was followed by Salvia divinorum (a plant containing a potent and selective κ receptor agonist) and a series of serotonergic psychedelics, including the endogenous serotonin 2A receptor agonist N,N-Dimethyltryptamine (DMT). This similarity was driven by semantic concepts related to consciousness of the self and the environment, but also by those associated with the therapeutic, ceremonial and religious aspects of drug use. Our analysis sheds light on the longstanding link between certain drugs and the experience of "dying", suggests that ketamine could be used as a safe and reversible experimental model for NDE phenomenology, and supports the speculation that endogenous NMDA antagonists with neuroprotective properties may be released in the proximity of death.

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Section: Introductionmentioning

confidence: 99%

Neurochemical models of near-death experiences: A large-scale study based on the semantic similarity of written reports

Martial

Cassol

Charland‐Verville

et al. 2019

Consciousness and Cognition

View full text Add to dashboard Cite

show abstract

“…In preclinical models, NMDAR antagonists blocked induction (36) and expression (41) of behavioral sensitization by stress, and blocked crosssensitization between stress and stimulants (36,43,44). In humans, intraoperative administration of NMDAR antagonist ketamine may reduce PTSD risk (54,55), and a single infusion of 0.5 mg/kg ketamine compared to midazolam in patients with PTSD resulted in rapid (within 24 h) and sustained (at least 7 days) improvement in PTSD symptoms (56,57). Finally, the lowaffinity NMDAR antagonist memantine improved hyperarousal and depressive symptoms in individuals with PTSD (58).…”

Section: Primary Outcome Measure: Biomarker Of Functional Mechanismmentioning

confidence: 99%

A Proof-of-Mechanism Study to Test Effects of the NMDA Receptor Antagonist Lanicemine on Behavioral Sensitization in Individuals With Symptoms of PTSD

et al. 2019

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Background: Individuals with post-traumatic stress disorder (PTSD) have a heightened sensitivity to subsequent stressors, addictive drugs, and symptom recurrence, a form of behavioral sensitization. N-methyl-D-aspartate receptors (NMDARs) are involved in the establishment and activation of sensitized behavior.Objective: We describe a protocol of a randomized placebo-controlled Phase 1b proofof-mechanism trial to examine target engagement, safety, tolerability, and possible efficacy of the NMDAR antagonist lanicemine in individuals with symptoms of PTSD (Clinician Administered PTSD Scale [CAPS-5] score ≥ 25) and evidence of behavioral sensitization measured as enhanced anxiety-potentiated startle (APS; T-score ≥ 2.8).Methods: Subjects (n = 24; age range 21-65) receive three 60-min intravenous infusions of placebo or 100 mg lanicemine over 5 non-consecutive days. Primary endpoint is change in APS from pre-treatment baseline to after the third infusion. NMDAR engagement is probed with resting state EEG gamma band power, 40 Hz auditory steady state response, the mismatch negativity amplitude, and P50 sensory gating. Change in CAPS-5 scores is an exploratory clinical endpoint. Bayesian statistical methods will evaluate endpoints to determine suitability of this agent for further study. Conclusion:In contrast to traditional early-phase trials that use symptom severity to track treatment efficacy, this study tracks engagement of the study drug on expression of behavioral sensitization, a functional mechanism likely to cut across disorders. This experimental therapeutics design is consistent with recent NIMH-industry collaborative Frontiers in Psychiatry | www.frontiersin.org STuDy PROTOCOL

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“…Wir haben Bedenken, durch Ketamin mögliche traumabedingte Dissoziationen zu verstärken. Es gibt Studien, die positive Effekte von Ketamin auf PTBS-Symptome beschreiben (36,37).…”

Section: Indikationsstellungunclassified

Ketamin in der Behandlung depressiver Episoden

Gilles¹,

Deuschle²

2018

Nervenheilkunde

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ZusammenfassungKetamin, ein hochaffiner nicht kompetitiver Antagonist am glutamatergen N-Methyl-D-Aspartat (NMDA-)Rezeptor zeigt potente und schnell wirksame antidepressive Effekte bei Patienten mit therapieresistenter unipolarer und bipolarer Depression. Dieser rasch einsetzende antidepressive Effekt konnte seit 2000 in vielen, wenn auch meist mit kleiner Fallzahl, randomisiert kontrollierten Studien gezeigt werden. Bis heute ist die Ketamingabe zur Behandlung depressiver Störungen eine Off-label-Behandlung. Behandlungsrichtlinien und -algorithmen im klinischen Umfeld sind ebenso wie mehr Forschung bezüglich der Beobachtung möglicher (nachteiliger) klinischer Langzeitwirkungen und Sicherheitsdaten von wiederholten Ketamingaben und -erhaltungstherapie nötig.

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Efficacy, Safety, and Durability of Repeated Ketamine Infusions for Comorbid Posttraumatic Stress Disorder and Treatment-Resistant Depression

Abstract: ClinicalTrials.gov identifier: NCT02577250.

Cited by 114 publications

References 27 publications

Neurochemical models of near-death experiences: A large-scale study based on the semantic similarity of written reports

Neurochemical models of near-death experiences: A large-scale study based on the semantic similarity of written reports

A Proof-of-Mechanism Study to Test Effects of the NMDA Receptor Antagonist Lanicemine on Behavioral Sensitization in Individuals With Symptoms of PTSD

Ketamin in der Behandlung depressiver Episoden

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