Ketamine for Depression: Advances in Clinical Treatment, Rapid Antidepressant Mechanisms of Action, and a Contrast with Serotonergic Psychedelics

Saelens, Johan; Kadriu, Bashkim; Zarate, Carlos A.; Kraus, Christoph

doi:10.1007/7854_2022_313

Cited by 4 publications

(4 citation statements)

References 153 publications

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“…While non-parenteral uses of ketamine require diligent monitoring by providers, abuse concerns should be weighed against the potential benefits of treatment. These findings are consistent with other research pointing to negligible risks of abuse associated with ketamine treatment of mood disorders in patients with no comorbid substance use disorders ( 21 ).…”

supporting

confidence: 92%

Editorial: Bridging the gap: an interdisciplinary perspective on ketamine in psychiatric disorders

Hartelius¹,

Muscat

Bartova

2023

Front. Psychiatry

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supporting

confidence: 92%

Editorial: Bridging the gap: an interdisciplinary perspective on ketamine in psychiatric disorders

Hartelius¹,

Muscat

Bartova

2023

Front. Psychiatry

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“…Its rationale for use in treating PTSD is similarly unclear. One such hypothesis proposes that ketamine facilitates the release of glutamate in the mPFC via NMDAR antagonism on GABAergic interneurons at subanesthetic doses [ 646 , 655 , 668 ] (Fig. 7 ).…”

Section: Psychedelics For the Treatment Of Ptsdmentioning

confidence: 99%

“…7 ). Glutamate subsequently binds to postsynaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs), stimulating an increase in brain-derived neurotrophic factor (BDNF), with downstream activation of the mammalian target of rapamycin (mTOR) [ 646 ] thereby inducing neuroplasticity and facilitating dendrite growth, potentially underlying ketamine’s therapeutic effects [ 668 ] (Fig. 7 ).…”

Section: Psychedelics For the Treatment Of Ptsdmentioning

confidence: 99%

The Psychedelic Future of Post-Traumatic Stress Disorder Treatment

Zaretsky,

Jagodnik,

Barsic

et al. 2024

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Post-traumatic stress disorder (PTSD) is a mental health condition that can occur following exposure to a traumatic experience. An estimated 12 million U.S. adults are presently affected by this disorder. Current treatments include psychological therapies (e.g., exposure-based interventions) and pharmacological treatments (e.g., selective serotonin reuptake inhibitors (SSRIs)). However, a significant proportion of patients receiving standard-of-care therapies for PTSD remain symptomatic, and new approaches for this and other trauma-related mental health conditions are greatly needed. Psychedelic compounds that alter cognition, perception, and mood are currently being examined for their efficacy in treating PTSD despite their current status as Drug Enforcement Administration (DEA)- scheduled substances. Initial clinical trials have demonstrated the potential value of psychedelicassisted therapy to treat PTSD and other psychiatric disorders. In this comprehensive review, we summarize the state of the science of PTSD clinical care, including current treatments and their shortcomings. We review clinical studies of psychedelic interventions to treat PTSD, trauma-related disorders, and common comorbidities. The classic psychedelics psilocybin, lysergic acid diethylamide (LSD), and N,N-dimethyltryptamine (DMT) and DMT-containing ayahuasca, as well as the entactogen 3,4-methylenedioxymethamphetamine (MDMA) and the dissociative anesthetic ketamine, are reviewed. For each drug, we present the history of use, psychological and somatic effects, pharmacology, and safety profile. The rationale and proposed mechanisms for use in treating PTSD and traumarelated disorders are discussed. This review concludes with an in-depth consideration of future directions for the psychiatric applications of psychedelics to maximize therapeutic benefit and minimize risk in individuals and communities impacted by trauma-related conditions.

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“…Ever since the first report of ketamine's antidepressant effects (1), there have also been some researchers who have attempted to bypass ketamine's psychoactive properties (2,3), but some degree of consciousness-alteration would generally occur (4). In this regard, the question whether ketamine's psychoactive effects are considered adverse or viewed as an inherent component of its therapeutic potential becomes increasingly important (4,5).…”

Section: Introductionmentioning

confidence: 99%

Case report: Maintaining altered states of consciousness over repeated ketamine infusions may be key to facilitate long-lasting antidepressant effects: some initial lessons from a personalized-dosing single-case study

Reissmann,

Hartmann,

Kist

et al. 2023

Front. Psychiatry

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BackgroundThe interest in psychoactive agents for treating mental disorders has gathered a growing body of scientific interest. However, research on the relationship between altered states of consciousness (ASCs) and ketamine’s antidepressant properties is still limited. Likewise, approaches to sustain early treatment success for the long-term are needed. Taking both aspects into account, the question arises whether the persistence of recurrent ASCs during the subsequent infusion sessions is crucial for the preservation of antidepressant effects during prolonged continued ketamine therapy.AimIn this case study we explored whether recurrent ASC experiences across a large number of infusions are associated with improved antidepressant effects in a single case study.MethodsA 62-year-old patient with treatment-resistant depression, who has been suffering from depressive episodes for over 20 years, was observed for 12 consecutive infusions across 16 weeks. ASCs during ketamine sessions were measured with the 5D-ASC, and pre/post-infusion depression scores with the BDI-II questionnaire. To emphasize psychoactive experiences a personalized antidepressant dose regimen was used.ResultsWe found a strong correlation between the experienced ASCs during ketamine infusions and the antidepressant effect: the stronger the ASCs overall, the stronger the resulting antidepressant effect. This correlation was consistently observed throughout the infusion series, independent of the number of ketamine sessions completed before. However, despite a personalized dose regimen, neither peri-infusion ASCs nor antidepressant effects could be established on a regular basis, leading overall to no improvement in treatment outcome.ConclusionMaintaining psychoactive effects over repeated ketamine infusions may be key to facilitate long-lasting antidepressant effects. However, for some depressed individuals maintenance of antidepressant effects and/or peri-infusion ASCs might not be achieved, even when personalized dosing is used.

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Ketamine for Depression: Advances in Clinical Treatment, Rapid Antidepressant Mechanisms of Action, and a Contrast with Serotonergic Psychedelics

Cited by 4 publications

References 153 publications

Editorial: Bridging the gap: an interdisciplinary perspective on ketamine in psychiatric disorders

Editorial: Bridging the gap: an interdisciplinary perspective on ketamine in psychiatric disorders

The Psychedelic Future of Post-Traumatic Stress Disorder Treatment

Case report: Maintaining altered states of consciousness over repeated ketamine infusions may be key to facilitate long-lasting antidepressant effects: some initial lessons from a personalized-dosing single-case study

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