Comparative effects of (S)-ketamine and racemic (R/S)-ketamine on psychopathology, state of consciousness and neurocognitive performance in healthy volunteers.
Torsten Passie, Hans-Anton Adams, Frank Logemann, Simon D. Brandt, Birgitt Wiese, Matthias Karst
European Neuropsychopharmacology March 2021 DOI: 10.1016/j.euroneuro.2021.01.005 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized double-blind placebo-controlled trial Peer reviewed |
|---|---|
| Sample size | 30 |
| Population | Healthy male volunteers |
| Interventions | (R/S)-ketamine (S)-ketamine placebo |
| Topics | Altered states of consciousness Esketamine Ketamine |
| Keywords | Anesthesia Neurocognition Psychopathology |
| Key findings | Both (R/S)-ketamine and (S)-ketamine produced significant psychopathology and neurocognitive impairment compared with placebo, with no significant differences between the two. Contrary to previous suggestions, (S)-ketamine did not show reduced psychopathological symptomatology compared with (R/S)-ketamine; the authors report a somewhat more negatively experienced psychopathology with (S)-ketamine and propose that (R)-ketamine may have protective effects against some psychotomimetic effects of (S)-ketamine. |
Abstract
Ketamine and its (S)-enantiomer show distinct psychological effects that are investigated in psychiatric research. Its antidepressant activity may depend on the extent and quality of these psychological effects which may greatly differ between the enantiomers. Previous data indicate that the (S)-ketamine isomer is a more potent anesthetic than (R)-ketamine. In contrast, in subanesthetic doses (R)-ketamine seems to elicit fewer dissociative and psychotomimetic effects compared to (S)-ketamine. In this randomized double-blind placebo-controlled trial the effects of (R/S)-ketamine and (S)-ketamine on standardized neuropsychological and psychopathological measures were compared. After an initial bolus equipotent subanesthetic doses of (R/S)- and (S)-ketamine or placebo were given by continuous intravenous infusion to three groups of 10 healthy male volunteers each (n = 30). (R/S)-Ketamine and (S)-ketamine produced significant psychopathology and neurocognitive impairment compared to placebo. No significant differences were found between (R/S)-ketamine and (S)-ketamine. (S)-Ketamine administration did not result in reduced psychopathological symptomatology compared to (R/S)-ketamine as suggested by previous studies. However, this study revealed a somewhat more "negatively experienced" psychopathology with (S)-ketamine, which opens questions about potential "protective effects" associated with the (R)-enantiomer against some psychotomimetic effects induced by the (S)-enantiomer. As the antidepressant effect of ketamine might depend on a pleasant experience of altered consciousness and perceptions and avoidance of anxiety, the ideal ketamine composition to treat depression should include (R)-ketamine. Moreover, since preclinical data indicate that (R)-ketamine is a more potent and longer acting antidepressant compared to (S)-ketamine and (R/S)-ketamine, randomized controlled trials on (R)-ketamine and comparative studies with (S)-ketamine and (R/S)-ketamine are eagerly awaited.
Comparable studies
Other randomized controlled trials on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans Healthy human subjects recruited from the community | 1994 | Randomized controlled trial | n = 19 |
| Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial Patients with treatment-resistant major depression experiencing a major depressive episode | 2013 | Randomized controlled trial | n = 73 |
| Remifentanil-induced Postoperative Hyperalgesia and Its Prevention with Small-dose Ketamine Patients undergoing major abdominal surgery | 2005 | Randomized controlled trial | n = 75 |
| Efficacy of Intravenous Ketamine for Treatment of Chronic Posttraumatic Stress Disorder Patients with chronic PTSD related to a range of trauma exposures | 2014 | Randomized controlled trial | n = 41 |
| Ketamine-Induced Deficits in Auditory and Visual Context-Dependent Processing in Healthy Volunteers Healthy volunteers | 2000 | Single-blind placebo-controlled study | n = 20 |
Citations in the library
Cited by 20
- Molecular mechanisms underlying the antidepressant actions of arketamine: beyond the NMDA receptor Molecular Psychiatry May 7, 2021
- Ketamine, Esketamine, and Arketamine: Their Mechanisms of Action and Applications in the Treatment of Depression and Alleviation of Depressive Symptoms. Biomedicines October 9, 2024
- Arketamine for cognitive impairment in psychiatric disorders European Archives of Psychiatry and Clinical Neuroscience February 14, 2023
- (R)-(-)-Ketamine: The Promise of a Novel Treatment for Psychiatric and Neurological Disorders. International Journal of Molecular Sciences June 20, 2024
- Repurposing Ketamine in Depression and Related Disorders: Can This Enigmatic Drug Achieve Success? Frontiers in Neuroscience April 30, 2021
and 15 more in the library
Cites 37
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms Pharmacological Reviews June 26, 2018
- Psychometric Evaluation of the Altered States of Consciousness Rating Scale (OAV) PLoS One August 31, 2010
- R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Translational Psychiatry September 1, 2015
- The Standardized Psychometric Assessment of Altered States of Consciousness (ASCs) in Humans Pharmacopsychiatry July 1, 1998
and 32 more in the library