Potential Antidepressive Effects of R-ketamine in Patients with Treatment Resistance Depression
Bibliographic record
Abstract
Ketamine has a long history as an anesthetic but has recently demonstrated antidepressant effects at sub-anesthetic doses (Matveychuk et al., 2020). For individuals with treatment-resistant depression (TRD), typical antidepressants are frequently ineffective, whereas ketamine’s unique mechanisms have demonstrated promising results in reducing depressive symptoms where other treatments have failed (Voineskos et al., 2020; Matveychuk et al., 2020). Pre-clinical investigation of the ketamine enantiomers, R- and S-ketamine, revealed that R-ketamine may be more effective than S-ketamine due to its rapid-acting, long-lasting antidepressant-like effects with fewer psychotomimetic side effects and abuse liability (Chang et al., 2019; Yang et al., 2015; Bonaventura et al., 2021; Koncz et al., 2023). However, early clinical trials assessing R-ketamine to treat TRD have not yet produced significant antidepressant effects despite promising safety and tolerability profiles (Leal et al., 2023). This review compares the antidepressant efficacy, abuse liability, and safety profiles of ketamine enantiomers, focusing on the antidepressant success of R-ketamine in pre-clinical and clinical trials for TRD. Although R-ketamine did present promising results for treating TRD in pre-clinical trials, it did not demonstrate consistent significant antidepressant effects in clinical trials, making it difficult to conclude its effects in treating depression.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".